Purpose: We successfully developed recombinant human interferon alpha-2b (rhIFN- α 2b) and mutein forms through the site-directed mutagenesis technique. The mutein forms were developed by substituting cysteins at positions 2 and 99 with aspartic acids. The potential adverse effects of these rhIFN- α 2bs were assessed by acute and subchronic studies.
Methods: In the acute study, rhIFN- α 2bs were subcutaneously administered to mice at a single dose of 97.5 μ g/kg, 975 μ g/kg, and 9.75 mg/kg BW and were observed for 14 days. In the subchronic study, single dose of 1.95 μ g/kg and 19.5 μ g/kg, respectively, was given subcutaneously every 3 days for 45 days.
Results: No death as well as abnormality in body weight, behavior, presentation of main organs, and value of plasma SGPT and SGOT was observed. Wild type and mutein rhIFN- α 2bs did not show significant adverse effects at dose up to 9.75 mg/kg BW. Administration of these rhIFN- α 2bs given repeatedly did not induce any adverse effect.
Conclusion: These results suggest that our rhIFN- α 2bs are safe. However, further study is still needed to clarify the safety issue before use in clinical trial.